The object of this project is to study the autonomic neuroendocrine control system for insulin and glucagon secretion, and to determine the role of abnormalites in this system in the pathogenesis of diabetes mellitus, hypoglycemia, and obesity. Studies are proposed in dogs, baboons, and in man. In dogs, insulin and glucagon secretory rates will be assessed in vivo using an extra corporeal flow system for the endocrine pancreas. The role of neural stimulation in the regulation of somatostatin secretion, and this interaction with insulin and glucagon secretion will be studied. The influence of insulin and glucagon secretion will be determined by measurement of cerebrospinal fluid levels in the basal state and after stimulation. The role of peptides in reflex control of the endocrine pancreas will be evaluated by the central infusion of peptides and measurements of pancreatic endocrine function. The mechanism of action of somatotropin release inhibiting factor (SRIF, somatostatin) on the secretion of pancreatic glucagon and insulin will be studied, and the ability to modulate its effects by neural factors determined. Studies of the effects of neural stimulation on endocrine pancreatic somatostatin release will also be performed. In baboons, it is proposed to examine the hypothesis that CSF hormone concentrations, particularly pancreatic peptides, comprise a feedback system for the regulation of body weight. The effects of central infusions of peptides will be studied in a chronic model for baboon feeding behavior and correlations made between circulating pancreatic hormone levels and nutrient ingestion. In man, the effects of surgical anesthesia and stress on pancreatic hormone secretion and plasma catecholamine levels will be determined. The role of adrenergic and prostaglandin-related inhibition of insulin secretion to insulin and glucagon secretion in normal subjects and diabetics will be tested. Inhibitors of catecholamine and prostaglandin action will be given to normal subjects and diabetics in both short-term and long-term studies of endocrine pancreatic function.